Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 1R01DA029078 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Institute on Drug Abuse (NIDA) | NIH |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Opioid medications are commonly used for pain relief. When given over time, physical dependence can occur. This results in unpleasant side effects (such as agitation and nausea) if opioid medications are suddenly stopped. This study aims to test the use of the drug ondansetron to reduce the symptoms associated with opioid withdrawal and to prevent the progression of opioid physical dependence, thereby allowing future investigators to better test the role of physical dependence in the development of addiction and also possibly improving acceptance of abstinence-based programs for addiction.
This study will be split into two separate investigations, aim 1 and aim 2.
Study aim 1 (Prevention of Opioid Withdrawal) will investigate whether ondansetron, a 5HT3-receptor antagonist, can reduce or prevent withdrawal signs and symptoms in patients physically dependent on opioids to treat chronic back pain. In this aim, study participants will be titrated onto sustained release oral morphine for 30 days after which time they will return to the lab to undergo naloxone-induced withdrawal with either 8 mg ondansetron pre-treatment (30 min prior to naloxone-induced withdrawal) or placebo. Participants will then return to their titrated dose of oral morphine for one week before returning for the second study session in which they will receive the opposite pre-treatment (8 mg ondansetron or placebo) 30 minutes prior to naloxone-induced withdrawal. Objective opioid withdrawal score (OOWS), subjective opioid withdrawal score (SOWS) and Profile of Mood States (POMS) will be assessed at baseline and five or seven times during the study sessions at 30 and 37 days post titration. Beck Depression Inventory, Roland-Morris Questionnaire and State-Trait Anxiety Inventory and VAS Pain Score will be assessed at baseline as well as at both study sessions (30 and 37 days post titration).
Study aim 2 (Prevention of Physical Dependence) will investigate whether ondansetron, a 5HT3 receptor antagonist, can prevent physical dependence in patients taking opioids chronically for controlling chronic back pain. Participants will taper onto sustained release oral morphine for 10 days then will maintain the effective dose for twenty days (total of 30 days) while simultaneously taking 8 mg ondansetron or placebo three times daily with morphine dose. After 30 days of morphine plus 8 mg ondansetron or placebo, study participants will return to the lab to undergo naloxone-induced withdrawal. OOWS, SOWS, POMS, pain visual analogue scale (VAS), Beck Depression Inventory and Roland Morris Disability Index will be administered at baseline and at the beginning of each study session (30 days post titration). Furthermore OOWS, SOWS and POMS will be administered twice during the first study session and at least five times during the second study session (Day 30): at the beginning of the session, after IV insertion, and after naloxone-induced opioid withdrawal.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prevention of Opioid Withdrawal | Experimental | Chronic back pain patients will titrate onto sustained release oral morphine for 30 days, and then will be randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (Naloxone 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may be administered at 0.8 mg/70 kg). Participants will return to their titrated morphine dose for one week and then return for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants will then taper back to their original dose of morphine for one week. |
|
| Prevention of Physical Dependence | Experimental | Chronic back pain patients will titrate onto sustained release oral morphine for 30 days; during morphine treatment, participants will be randomized to take either ondansetron 8 mg or matching placebo three times daily along with the oral morphine treatment. After thirty days, participants will return to the lab to undergo naloxone-induced withdrawal in clinic (Naloxone 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may be administered at 0.8 mg/70 kg). Participants will then taper back to their original dose of morphine for one week. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ondansetron | Drug | Ondansetron 8 mg oral tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Objective Opioid Withdrawal Score (OOWS) From Baseline (Prevention of Opioid Withdrawal) | Originally developed by Handelsman, the Objective Opioid Withdrawal Scale (OOWS) score is a well-characterized measure of opioid withdrawal in humans, calculated as the sum of a 13-item physician assessment documenting physically observable signs of withdrawal, which are rated as present (1) or absent (0) during the observation period. The minimum score of 0 means the patient is not showing any signs of opioid withdrawal. The maximum score of 13 signifies all signs of opioid withdrawal to the largest extent possible. Immediately prior to ondansetron or placebo administration a baseline OOWS score was taken. 30 minutes later participants received naloxone, then 15 minutes later an OOWS score was taken. If deemed necessary by the clinician, participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an OOWS score was taken. Change from the baseline OOWS score to the score assessed following the last naloxone dose is reported. | Baseline; 15 minutes following last naloxone dose |
| Change in Objective Opioid Withdrawal Score From Baseline (Prevention of Physical Dependence) | Originally developed by Handelsman, the OOWS score is a well-characterized measure of opioid withdrawal in humans, calculated as the sum of a 13-item physician assessment documenting physically observable signs of withdrawal, which are rated as present (1) or absent (0) during the observation period. The maximum score is 13 and suggests the patient is showing all signs of opioid withdrawal to the largest extent possible. The minimum score of 0 suggests the patient is not showing any signs of opioid withdrawal. Immediately prior to ondansetron or placebo administration a baseline OOWS score was taken. 30 minutes later participants received naloxone, then 15 minutes later an OOWS score was taken. If necessary (as deemed by the clinician), participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an OOWS score was taken. Change from the baseline OOWS score to the score assessed following the last naloxone dose is reported. | Baseline; 15 minutes following last naloxone dose |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Subjective Opioid Withdrawal Score (SOWS) From Baseline (Prevention of Opioid Withdrawal) | The Subjective Opioid Withdrawal Score (SOWS) score is calculated as the sum of 16 subjective patient-reported symptom scores rated on a scale of 0 to 4 (0=not at all, 4=extremely) based on what subjects were experiencing at the time of testing. A maximum score of 64 would suggest the patient is experiencing the symptoms of withdrawal to the maximum extent possible while the lowest score of 0 would suggest the patient is not experiencing any of the symptoms of withdrawal. Immediately prior to ondansetron or placebo administration a baseline SOWS score was taken. 30 minutes later participants received naloxone, then 15 minutes later an SOWS score was taken. If necessary (as deemed by the clinician), participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an SOWS score was taken. Change from the baseline SOWS score to the score assessed following the last naloxone dose is reported |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Larry F Chu, MD, MS | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University | Stanford | California | 94305 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19214139 | Background | Chu LF, Liang DY, Li X, Sahbaie P, D'arcy N, Liao G, Peltz G, David Clark J. From mouse to man: the 5-HT3 receptor modulates physical dependence on opioid narcotics. Pharmacogenet Genomics. 2009 Mar;19(3):193-205. doi: 10.1097/FPC.0b013e328322e73d. | |
| 12635113 | Background | Atlas SJ, Nardin RA. Evaluation and treatment of low back pain: an evidence-based approach to clinical care. Muscle Nerve. 2003 Mar;27(3):265-84. doi: 10.1002/mus.10311. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
No enrolled participants were excluded from the study after enrollment and before assignment to groups.
Chronic back pain patients were recruited from the San Francisco Bay Area via recruitment posters, newspaper advertisements, and radio and television announcements.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Prevention of Opioid Withdrawal-Ondansetron | Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may be administered at 0.8 mg/70 kg). Participants returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week. Data regarding how many participants received ondansetron first versus placebo first are not accessible. |
| FG001 | Prevention of Opioid Withdrawal-Placebo | Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may be administered at 0.8 mg/70 kg). Participants returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week. Data regarding how many participants received ondansetron first versus placebo first are not accessible. |
| FG002 | Prevention of Physical Dependence - Ondansetron | Chronic back pain patients titrated onto sustained release oral morphine for 30 days; during morphine treatment, participants were randomized to take either ondansetron 8 mg or matching placebo three times daily along with the oral morphine treatment. After thirty days, participants returned to the lab to undergo naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may have been administered at 0.8 mg/70 kg). Participants then tapered back to their original dose of morphine for one week. |
| FG003 | Prevention of Physical Dependence - Placebo | Chronic back pain patients titrated onto sustained release oral morphine for 30 days; during morphine treatment, participants were randomized to take either ondansetron 8 mg or matching placebo three times daily along with the oral morphine treatment. After thirty days, participants returned to the lab to undergo naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may have been administered at 0.8 mg/70 kg). Participants then tapered back to their original dose of morphine for one week. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participants that completed the protocol are included in the analysis
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Prevention of Opioid Withdrawal | Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may be administered at 0.8 mg/70 kg). Participants returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week. Data regarding how many participants received ondansetron first versus placebo first are not accessible. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Objective Opioid Withdrawal Score (OOWS) From Baseline (Prevention of Opioid Withdrawal) | Originally developed by Handelsman, the Objective Opioid Withdrawal Scale (OOWS) score is a well-characterized measure of opioid withdrawal in humans, calculated as the sum of a 13-item physician assessment documenting physically observable signs of withdrawal, which are rated as present (1) or absent (0) during the observation period. The minimum score of 0 means the patient is not showing any signs of opioid withdrawal. The maximum score of 13 signifies all signs of opioid withdrawal to the largest extent possible. Immediately prior to ondansetron or placebo administration a baseline OOWS score was taken. 30 minutes later participants received naloxone, then 15 minutes later an OOWS score was taken. If deemed necessary by the clinician, participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an OOWS score was taken. Change from the baseline OOWS score to the score assessed following the last naloxone dose is reported. | Participants in the Prevention of Opioid Withdrawal Arm were analyzed. | Posted | Mean | Standard Deviation | units on a scale | Baseline; 15 minutes following last naloxone dose |
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Prevention of Opioid Withdrawal | Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may be administered at 0.8 mg/70 kg). Participants returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week. |
Not provided
Not provided
Aim 1: Use of a single 8mg dose of ondansetron as well as a lack of biochemical data is a limitation of this study.
Aim 2: Use of 8mg of ondansetron instead of varying doses is a limitation of this study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Larry F. Chu | Stanford University School of Medicine Department of Anesthesiology | 6507236632 | lchu@stanford.edu |
Not provided
| ID | Term |
|---|---|
| D017294 | Ondansetron |
| D009020 | Morphine |
| D009270 | Naloxone |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | Placebo to Match Ondansetron |
|
| Morphine | Drug | Sustained release oral morphine, beginning at 30 mg/d, titrated up by 15 mg/d every 2 days until adequate analgesia is achieved |
|
| Naloxone 0.4 mg/70 kg | Drug | Naloxone 0.4 mg/70 kg intravenous |
|
| Naloxone 0.8 mg/70 kg | Drug | Naloxone 0.8 mg/70 kg intravenous |
|
| Baseline; 15 minutes following last naloxone dose |
| Beck Depression Inventory Score (BDIS) Change From Baseline (Prevention of Opioid Withdrawal) | The Beck Depression Inventory (a 21-item self-report multiple-choice inventory) yields a single summed score between 0 and 63; higher scores indicate more severe depression. Change is from baseline score (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken prior to receiving ondansetron or placebo, at the beginning of second study visit). | 2 study days 1 month apart (at the start of each study visit) |
| Profile of Mood States (POMS) Change in Score From Baseline (Prevention of Opioid Withdrawal) | Profile of Mood States (POMS) is a 65-question survey of how participants have been feeling over the past week, assessing tension, depression, anger, fatigue, confusion and vigor. Each question is on a 5-point scale: 0 (not at all) to 4 (extremely). Overall score range: 0 to 200 (lower scores corresponding to fewer symptoms), calculated by adding total scores for tension, depression, anger, fatigue and confusing, and subtracting that total score from the total score for vigor. Immediately prior to ondansetron or placebo administration a baseline POMS score was taken. 30 minutes later participants received naloxone, then 15 minutes later a POMS score was taken. If necessary (as deemed by the clinician), participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an POMS score was taken. Change from the baseline POMS score to the score assessed following the last naloxone dose is reported. | Baseline; 15 minutes following last naloxone dose |
| Change in Pain Visual Analog Scale (VAS) From Baseline (Prevention of Opioid Withdrawal) | The VAS is a 0 to 100 millimeter scale where 0 corresponds to no pain and 100 to extreme pain, used by participants to indicated their level of pain over the last two weeks. Change is from baseline score for average level of pain (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken prior to receiving ondansetron or placebo, at the beginning of second study visit). | 2 study days 1 month apart (at the start of each study visit) |
| Change in Roland-Morris Disability Index (RMDI) From Baseline (Prevention of Opioid Withdrawal) | The Roland-Morris Disability Index is a 24-question instrument used to assess level of disability from lower back pain. Scores range from 0-24 with lower scores corresponding to fewer symptoms. Change is from baseline score (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken prior to receiving ondansetron or placebo, at the beginning of second study visit). | 2 study days 1 month apart (at the start of each study visit) |
| Change in Subjective Opioid Withdrawal Score From Baseline (Prevention of Physical Dependence) | The SOWS score is composed of 16 subjective symptoms rated on a scale of 0 to 4 (0=not at all, 4=extremely) based on what subjects were experiencing at the time of testing. A maximum score of 64 would suggest the patient is experiencing the symptoms of withdrawal to the maximum extent possible while the lowest score of 0 would suggest the patient is not experiencing any of the symptoms of withdrawal. Immediately prior to ondansetron or placebo administration a baseline SOWS score was taken. 30 minutes later participants received naloxone, then 15 minutes later an SOWS score was taken. If necessary (as deemed by the clinician), participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an SOWS score was taken. Change from the baseline SOWS score to the score assessed following the last naloxone dose is reported | Baseline; 15 minutes following last naloxone dose |
| Beck Depression Inventory Score (BDIS) Change From Baseline (Prevention of Physical Dependence) | The Beck Depression Inventory (a 21-item self-report multiple-choice inventory) yields a single summed score between 0 and 63; higher scores indicate more severe depression. Change is from baseline score (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken at the beginning of second study visit). | 2 study days 1 month apart (at the start of each study visit) |
| Profile of Mood States (POMS) Change in Score From Baseline (Prevention of Physical Dependence) | (Profile of Mood States) POMS is a 65-question survey of how participants have been feeling over the past week, assessing tension, depression, anger, fatigue, confusion and vigor. Each question is on a 5-point scale: 0 (not at all) to 4 (extremely). Overall score range: 0 to 200 (lower scores corresponding to fewer symptoms), calculated by adding total scores for tension, depression, anger, fatigue and confusing, and subtracting that total score from the total score for vigor. Immediately prior to ondansetron or placebo administration a baseline POMS score was taken. 30 minutes later participants received naloxone, then 15 minutes later a POMS score was taken. If necessary (as deemed by the clinician), participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an POMS score was taken. Change from the baseline POMS score to the score assessed following the last naloxone dose is reported. | Baseline; 15 minutes following last naloxone dose |
| Change in Pain Visual Analog Scale (VAS) From Baseline (Prevention of Physical Dependence) | The VAS is a 0 to 100 millimeter scale where 0 corresponds to no pain and 100 to extreme pain, used by participants to indicated their level of pain over the last two weeks. Change is from baseline score for average level of pain (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken at the beginning of second study visit). | 2 study days 1 month apart (at the start of each study visit) |
| Change in Roland-Morris Disability (RMDI) Index From Baseline (Prevention of Physical Dependence) | The Roland-Morris Disability Index is a 24-question instrument used to assess level of disability from lower back pain. Scores range from 0-24 with lower scores corresponding to fewer symptoms. Change is from baseline score (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken at the beginning of second study visit). | 2 study days 1 month apart (at the start of each study visit) |
| 23964897 | Background | Betses M, Brennan T. Abusive prescribing of controlled substances--a pharmacy view. N Engl J Med. 2013 Sep 12;369(11):989-91. doi: 10.1056/NEJMp1308222. Epub 2013 Aug 21. No abstract available. |
| 21392250 | Background | Birnbaum HG, White AG, Schiller M, Waldman T, Cleveland JM, Roland CL. Societal costs of prescription opioid abuse, dependence, and misuse in the United States. Pain Med. 2011 Apr;12(4):657-67. doi: 10.1111/j.1526-4637.2011.01075.x. Epub 2011 Mar 10. |
| 22704854 | Background | Chu LF, D'Arcy N, Brady C, Zamora AK, Young CA, Kim JE, Clemenson AM, Angst MS, Clark DJ. Analgesic tolerance without demonstrable opioid-induced hyperalgesia: a double-blinded, randomized, placebo-controlled trial of sustained-release morphine for treatment of chronic nonradicular low-back pain. Pain. 2012 Aug;153(8):1583-1592. doi: 10.1016/j.pain.2012.02.028. Epub 2012 Jun 16. |
| 11844633 | Background | Clark JD. Chronic pain prevalence and analgesic prescribing in a general medical population. J Pain Symptom Manage. 2002 Feb;23(2):131-7. doi: 10.1016/s0885-3924(01)00396-7. |
| 1839313 | Background | Colthup PV, Felgate CC, Palmer JL, Scully NL. Determination of ondansetron in plasma and its pharmacokinetics in the young and elderly. J Pharm Sci. 1991 Sep;80(9):868-71. doi: 10.1002/jps.2600800913. |
| 14636819 | Background | Compton P, Athanasos P, Elashoff D. Withdrawal hyperalgesia after acute opioid physical dependence in nonaddicted humans: a preliminary study. J Pain. 2003 Nov;4(9):511-9. doi: 10.1016/j.jpain.2003.08.003. |
| 14751453 | Background | Compton P, Miotto K, Elashoff D. Precipitated opioid withdrawal across acute physical dependence induction methods. Pharmacol Biochem Behav. 2004 Feb;77(2):263-8. doi: 10.1016/j.pbb.2003.10.017. |
| 3687892 | Background | Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD. Two new rating scales for opiate withdrawal. Am J Drug Alcohol Abuse. 1987;13(3):293-308. doi: 10.3109/00952998709001515. |
| 10147044 | Background | Plosker GL, Milne RJ. Ondansetron: a pharmacoeconomic and quality-of-life evaluation of its antiemetic activity in patients receiving cancer chemotherapy. Pharmacoeconomics. 1992 Oct;2(4):285-304. doi: 10.2165/00019053-199202040-00005. |
| 8517886 | Background | Meert TF. Effects of various serotonergic agents on alcohol intake and alcohol preference in Wistar rats selected at two different levels of alcohol preference. Alcohol Alcohol. 1993 Mar;28(2):157-70. |
| 28514235 | Result | Chu LF, Sun J, Clemenson A, Erlendson MJ, Rico T, Cornell E, Obasi H, Sayyid ZN, Encisco EM, Yu J, Gamble JG, Carroll I, Clark JD. Ondansetron Does Not Reduce Withdrawal in Patients With Physical Dependence on Chronic Opioid Therapy. J Addict Med. 2017 Sep/Oct;11(5):342-349. doi: 10.1097/ADM.0000000000000321. |
| 29278818 | Result | Chu LF, Rico T, Cornell E, Obasi H, Encisco EM, Vertelney H, Gamble JG, Crawford CW, Sun J, Clemenson A, Erlendson MJ, Okada R, Carroll I, Clark JD. Ondansetron does not prevent physical dependence in patients taking opioid medications chronically for pain control. Drug Alcohol Depend. 2018 Feb 1;183:176-183. doi: 10.1016/j.drugalcdep.2017.06.043. Epub 2017 Aug 14. |
| Study Drug Titration Failure |
|
| Withdrawal Effect |
|
| Did Not Return Due to Withdrawal Effect |
|
| Problem with Infusion |
|
| Titration Non-Compliance |
|
| Titration Side Effects |
|
| Withdrawal by Subject |
|
| BG001 | Prevention of Physical Dependence-Ondansetron | Chronic back pain patients titrated onto sustained release oral morphine for 30 days; during morphine treatment, participants were randomized to take either ondansetron 8 mg or matching placebo three times daily along with the oral morphine treatment. After thirty days, participants returned to the lab to undergo naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may have been administered at 0.8 mg/70 kg). Participants then tapered back to their original dose of morphine for one week. |
| BG002 | Prevention of Physical Dependence-Placebo | Chronic back pain patients titrated onto sustained release oral morphine for 30 days; during morphine treatment, participants were randomized to take either ondansetron 8 mg or matching placebo three times daily along with the oral morphine treatment. After thirty days, participants returned to the lab to undergo naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may have been administered at 0.8 mg/70 kg). Participants then tapered back to their original dose of morphine for one week. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Prevention of Opioid Withdrawal | Chronic back pain patients titrated onto sustained release oral morphine for 30 days, then were randomized to take either ondansetron 8 mg or matching placebo thirty minutes prior to naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may be administered at 0.8 mg/70 kg). Participants returned to their titrated morphine dose for one week and then returned for the opposite pre-treatment followed by naloxone-induced withdrawal in clinic. Participants then tapered back to their original dose of morphine for one week. |
|
|
|
| Secondary | Change in Subjective Opioid Withdrawal Score (SOWS) From Baseline (Prevention of Opioid Withdrawal) | The Subjective Opioid Withdrawal Score (SOWS) score is calculated as the sum of 16 subjective patient-reported symptom scores rated on a scale of 0 to 4 (0=not at all, 4=extremely) based on what subjects were experiencing at the time of testing. A maximum score of 64 would suggest the patient is experiencing the symptoms of withdrawal to the maximum extent possible while the lowest score of 0 would suggest the patient is not experiencing any of the symptoms of withdrawal. Immediately prior to ondansetron or placebo administration a baseline SOWS score was taken. 30 minutes later participants received naloxone, then 15 minutes later an SOWS score was taken. If necessary (as deemed by the clinician), participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an SOWS score was taken. Change from the baseline SOWS score to the score assessed following the last naloxone dose is reported | Participants in the Prevention of Opioid Withdrawal Arm were analyzed. | Posted | Mean | Standard Deviation | units on a scale | Baseline; 15 minutes following last naloxone dose |
|
|
|
|
| Secondary | Beck Depression Inventory Score (BDIS) Change From Baseline (Prevention of Opioid Withdrawal) | The Beck Depression Inventory (a 21-item self-report multiple-choice inventory) yields a single summed score between 0 and 63; higher scores indicate more severe depression. Change is from baseline score (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken prior to receiving ondansetron or placebo, at the beginning of second study visit). | Participants in the Prevention of Opioid Withdrawal Arm were analyzed. | Posted | Mean | Standard Deviation | units on a scale | 2 study days 1 month apart (at the start of each study visit) |
|
|
|
|
| Secondary | Profile of Mood States (POMS) Change in Score From Baseline (Prevention of Opioid Withdrawal) | Profile of Mood States (POMS) is a 65-question survey of how participants have been feeling over the past week, assessing tension, depression, anger, fatigue, confusion and vigor. Each question is on a 5-point scale: 0 (not at all) to 4 (extremely). Overall score range: 0 to 200 (lower scores corresponding to fewer symptoms), calculated by adding total scores for tension, depression, anger, fatigue and confusing, and subtracting that total score from the total score for vigor. Immediately prior to ondansetron or placebo administration a baseline POMS score was taken. 30 minutes later participants received naloxone, then 15 minutes later a POMS score was taken. If necessary (as deemed by the clinician), participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an POMS score was taken. Change from the baseline POMS score to the score assessed following the last naloxone dose is reported. | Participants in the Prevention of Opioid Withdrawal Arm were analyzed. | Posted | Mean | Standard Deviation | units on a scale | Baseline; 15 minutes following last naloxone dose |
|
|
|
|
| Secondary | Change in Pain Visual Analog Scale (VAS) From Baseline (Prevention of Opioid Withdrawal) | The VAS is a 0 to 100 millimeter scale where 0 corresponds to no pain and 100 to extreme pain, used by participants to indicated their level of pain over the last two weeks. Change is from baseline score for average level of pain (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken prior to receiving ondansetron or placebo, at the beginning of second study visit). | Participants in the Prevention of Opioid Withdrawal Arm were analyzed. | Posted | Mean | Standard Deviation | units on a scale | 2 study days 1 month apart (at the start of each study visit) |
|
|
|
|
| Secondary | Change in Roland-Morris Disability Index (RMDI) From Baseline (Prevention of Opioid Withdrawal) | The Roland-Morris Disability Index is a 24-question instrument used to assess level of disability from lower back pain. Scores range from 0-24 with lower scores corresponding to fewer symptoms. Change is from baseline score (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken prior to receiving ondansetron or placebo, at the beginning of second study visit). | Participants in the Prevention of Opioid Withdrawal Arm were analyzed. | Posted | Mean | Standard Deviation | units on a scale | 2 study days 1 month apart (at the start of each study visit) |
|
|
|
|
| Primary | Change in Objective Opioid Withdrawal Score From Baseline (Prevention of Physical Dependence) | Originally developed by Handelsman, the OOWS score is a well-characterized measure of opioid withdrawal in humans, calculated as the sum of a 13-item physician assessment documenting physically observable signs of withdrawal, which are rated as present (1) or absent (0) during the observation period. The maximum score is 13 and suggests the patient is showing all signs of opioid withdrawal to the largest extent possible. The minimum score of 0 suggests the patient is not showing any signs of opioid withdrawal. Immediately prior to ondansetron or placebo administration a baseline OOWS score was taken. 30 minutes later participants received naloxone, then 15 minutes later an OOWS score was taken. If necessary (as deemed by the clinician), participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an OOWS score was taken. Change from the baseline OOWS score to the score assessed following the last naloxone dose is reported. | Participants in the Prevention of Physical Dependence Arm were analyzed. | Posted | Mean | Standard Deviation | units on a scale | Baseline; 15 minutes following last naloxone dose |
|
|
|
|
| Secondary | Change in Subjective Opioid Withdrawal Score From Baseline (Prevention of Physical Dependence) | The SOWS score is composed of 16 subjective symptoms rated on a scale of 0 to 4 (0=not at all, 4=extremely) based on what subjects were experiencing at the time of testing. A maximum score of 64 would suggest the patient is experiencing the symptoms of withdrawal to the maximum extent possible while the lowest score of 0 would suggest the patient is not experiencing any of the symptoms of withdrawal. Immediately prior to ondansetron or placebo administration a baseline SOWS score was taken. 30 minutes later participants received naloxone, then 15 minutes later an SOWS score was taken. If necessary (as deemed by the clinician), participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an SOWS score was taken. Change from the baseline SOWS score to the score assessed following the last naloxone dose is reported | Participants in the Prevention of Physical Dependence Arm were analyzed. | Posted | Mean | Standard Deviation | units on a scale | Baseline; 15 minutes following last naloxone dose |
|
|
|
|
| Secondary | Beck Depression Inventory Score (BDIS) Change From Baseline (Prevention of Physical Dependence) | The Beck Depression Inventory (a 21-item self-report multiple-choice inventory) yields a single summed score between 0 and 63; higher scores indicate more severe depression. Change is from baseline score (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken at the beginning of second study visit). | Participants in the Prevention of Physical Dependence Arm were analyzed. | Posted | Mean | Standard Deviation | units on a scale | 2 study days 1 month apart (at the start of each study visit) |
|
|
|
|
| Secondary | Profile of Mood States (POMS) Change in Score From Baseline (Prevention of Physical Dependence) | (Profile of Mood States) POMS is a 65-question survey of how participants have been feeling over the past week, assessing tension, depression, anger, fatigue, confusion and vigor. Each question is on a 5-point scale: 0 (not at all) to 4 (extremely). Overall score range: 0 to 200 (lower scores corresponding to fewer symptoms), calculated by adding total scores for tension, depression, anger, fatigue and confusing, and subtracting that total score from the total score for vigor. Immediately prior to ondansetron or placebo administration a baseline POMS score was taken. 30 minutes later participants received naloxone, then 15 minutes later a POMS score was taken. If necessary (as deemed by the clinician), participants may have received a second naloxone dose (25 minutes following 1st naloxone dose), then 15 minutes later an POMS score was taken. Change from the baseline POMS score to the score assessed following the last naloxone dose is reported. | Participants in the Prevention of Physical Dependence Arm were analyzed. | Posted | Mean | Standard Deviation | units on a scale | Baseline; 15 minutes following last naloxone dose |
|
|
|
|
| Secondary | Change in Pain Visual Analog Scale (VAS) From Baseline (Prevention of Physical Dependence) | The VAS is a 0 to 100 millimeter scale where 0 corresponds to no pain and 100 to extreme pain, used by participants to indicated their level of pain over the last two weeks. Change is from baseline score for average level of pain (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken at the beginning of second study visit). | Participants in the Prevention of Physical Dependence Arm were analyzed. | Posted | Mean | Standard Deviation | units on a scale | 2 study days 1 month apart (at the start of each study visit) |
|
|
|
|
| Secondary | Change in Roland-Morris Disability (RMDI) Index From Baseline (Prevention of Physical Dependence) | The Roland-Morris Disability Index is a 24-question instrument used to assess level of disability from lower back pain. Scores range from 0-24 with lower scores corresponding to fewer symptoms. Change is from baseline score (taken at the beginning of the first study visit, prior to beginning of titration into morphine) to the score taken after taking morphine for 30 days (score taken at the beginning of second study visit). | Participants in the Prevention of Physical Dependence Arm were analyzed. | Posted | Mean | Standard Deviation | units on a scale | 2 study days 1 month apart (at the start of each study visit) |
|
|
|
|
| 0 |
| 33 |
| 0 |
| 33 |
| EG001 | Prevention of Physical Dependence | Chronic back pain patients titrated onto sustained release oral morphine for 30 days; during morphine treatment, participants were randomized to take either ondansetron 8 mg or matching placebo three times daily along with the oral morphine treatment. After thirty days, participants returned to the lab to undergo naloxone-induced withdrawal in clinic (naloxone dose: 0.4 mg/70 kg; if deemed necessary by the clinician to induce withdrawal, a second naloxone dose may have been administered at 0.8 mg/70 kg). Participants then tapered back to their original dose of morphine for one week. | 0 | 48 | 0 | 48 |
Not provided
Not provided
Not provided
| D002227 |
| Carbazoles |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |
|
|
|
|
|
|